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PRACTICAL USAGE OF ANTIBACTERIAL AGENTS

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PRACTICAL USAGE OF ANTIBACTERIAL AGENTS Rema Merhi, D.O. PGY-3 Infectious Disease University of Nevada School of Medicine Pisespong Patamasucon, M.D. – PowerPoint PPT presentation

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Title: PRACTICAL USAGE OF ANTIBACTERIAL AGENTS


1
PRACTICAL USAGE OF ANTIBACTERIAL AGENTS
  • Rema Merhi, D.O.
  • PGY-3
  • Infectious Disease
  • University of Nevada School of Medicine
  • Pisespong Patamasucon, M.D.
  • Professor of Pediatrics
  • Director Pediatric Infectious Diseases
  • University of Nevada School of Medicine

2
  • Penicillins

3
Carbenicillin Ticarcillin
Piperacillin
Ampicillin
Ampicillin Sulbactam Ampicillin
Clavulanate Ticarcillin Clavulanate Piperacillin
Tazobactam
Nafcillin Oxacillin Methicillin
4
Penicillin
  • Gram-Positive Cocci
  • Streptococci
  • Except Enterococcus
  • Gram-Positive Rods
  • C. diphtheria
  • Gram-Negative Cocci
  • Neisseria
  • Spirochete
  • Treponema pallidum
  • Anerobic
  • Except Bacteroides fragilis

No Gram Negative Rod Coverage Amino-penicillin

5
Gram Negative
Carbenicillin Ticarcillin
Piperacillin (low Na load)
Ampicillin
E.coli, Shigella, Proteus, Salmonella, Listeria,
H.influ, Klebsiella
Pseudomonas, B. fragilis
GPC, GPR, GNC, SpirocheteAnaerobes
Ampicillin Sulbactam Ampicillin
Clavulanate Ticarcillin Clavulanate Piperacillin
Tazobactam
Nafcillin Oxacillin Methicillin
Staphylococci (MSSA) increased anaerobic
coverage
Staphylococci (MSSA)
6
  • Cephalosporins

7
Cephalosporin
  • Same mechanism as penicillin
  • If allergic to PCN? can react to this too!
  • Bacteriostatic
  • Does not cover
  • L- listeria
  • A- anaerobes
  • M- MRSA
  • E- enterococcus
  • Cefoxitin, Cefotetan cover anaerobes

8
1st Generation Cephalosporin (except H. influ)
Gram Negative
Carbenicillin Ticarcillin
Piperacillin
Ampicillin
E.coli, Shigella, Proteus, Salmonella, Listeria,
H.influ, Klebsiella
Pseudomonas, B.fragilis
GPC, GPR, GNC, SpirocheteAnaerobes
Ampicillin Sulbactam Ampicillin
Clavulanate Ticarcillin Clavulanate Piperacillin
Tazobactam
Nafcillin Oxacillin Methicillin
Staphylococci (MSSA)
Staphylococci (MSSA)
9
Cephalosporin
  • 1st Generation
  • Gram Positive
  • S. aureus, S. epidermidis, Streptococcus species
  • NO MRSA
  • Gram Negative
  • E. coli, K. pneumoniae, P. mirabilis
  • NO Enterococci
  • Anaerobes
  • NO B. fragilis

10
Cephalosporin
  • 1st Generation
  • Cefazolin (Ancef)
  • IV
  • Given q 8º
  • Surgery prophylaxis
  • Cephalexin (Keflex)
  • PO
  • Skin? 50mg/kg/day
  • Bone? 2-3x skin dose
  • Cefadroxil (Duricef)
  • PO
  • Given q 12º
  • UTI
  • Especially for ampicillin and TMP/SMZ resistant

11
  • 2nd Generation Cephalosporin

12
2nd Generation Cephalosporin (including H. influ)
Gram Negative
Carbenicillin Ticarcillin
Piperacillin
Ampicillin
E.coli, Shigella, Proteus, Salmonella, Listeria,
H.influ, Klebsiella
Pseudomonas, B. fragilis
GPC, GPR, GNC, SpirocheteAnaerobes
Ampicillin Sulbactam Ampicillin
Clavulanate Ticarcillin Clavulanate Piperacillin
Tazobactam
Nafcillin Oxacillin Methicillin
Staphylococci (MSSA)
Staphylococci (MSSA)
13
Cephalosporin
  • 2nd Generation
  • Less GM coverage, More GNB coverage
  • Beta-Lactamase / Beta-Lactamase
  • Add H.influ (with BL and -), Enterobacter,
    Neisseria
  • CNS penetration lt than 3rd generation
  • Cefuroxime
  • CNS penetration
  • Cefoxitin
  • Anaerobic coverage!
  • Surgeons/ OB-GYNs
  • Cefotetan
  • Anaerobic coverage!
  • GN coverage (PID)

14
  • 3rd Generation Cephalosporin

15
3rd Generation Cephalosporin
Gram Negative
Carbenicillin Ticarcillin
Piperacillin
Ampicillin
E.Coli, Shigella, Proteus, Salmonella, Listeria,
H.influ, Klebsiella
Pseudomonas, B.fragilis
GPC, GPR, GNC, SpirocheteAnaerobes
Nafcillin Oxacillin Methicillin
Ampicillin Sulbactam Ampicillin
Clavulanate Ticarcillin Clavulanate Piperacillin
Tazobactam
Staphylococci (MSSA)
Staphylococci (MSSA)
16
Cephalosporin
  • 3rd Generation
  • Great GN coverage No staph coverage
  • CNS coverage
  • Ceftriaxone
  • IV q 24º
  • CNS penetration
  • High activity against beta-lactamase producing
    H.influ, N.gonorrhoeae
  • Cefotaxime
  • IV q 6º
  • CNS penetration
  • High activity against beta-lactamase producing
    H.influ, N.gonorrhoeae
  • Ceftazidime
  • Antipseudomonal

17
3rd Generation Cephalosporins
Gram Negative
1st Generation Cephalosporins (except H. influ)
Carbenicillin Ticarcillin
Piperacillin
Ampicillin
E.Coli, Shigella, Proteus, Salmonella, Listeria,
H.influ
Pseudomonas, B.fragilis
2nd Generation Cephalosporins (including H. influ)
GPC, GPR, GNC, SpirocheteAnerobes
Ampicillin Sulbactam Ampicillin
Clavulanate Ticarcillin Clavulanate Piperacillin
Tazobactam
Nafcillin Oxacillin Methicillin
Staphylococci (MSSA)
Staphylococci (MSSA)
18
Cephalosporin
  • 4th Generation
  • Cefepime- pseudomonas
  • Covers GN
  • Nosocomial GNB? acinobacter
  • S. pneumo
  • Does NOT cover Extended Spectrum Beta-Lactamase
  • ESBLs

19
ESBLs
  • Extended Spectrum Beta-Lactamases
  • Enterococcus faecium
  • Serratia
  • Klebsiella pneumoniae
  • Acinetobacter baumanii
  • Providencia/pseudomonas
  • Enterobacter spp.
  • Salmonella, E. coli
  • Treatment
  • Meropenem
  • PipercillinTazobactam
  • Zosyn

20
Side Effects
  • Penicillin
  • Black or hairy tongue
  • Exaggerated reflexes
  • Mild diarrhea
  • Nausea or vomiting
  • Pain, swelling, or redness at the injection site
  • Twitching
  • Anaphylaxis

21
Side Effects
  • Cephalosporins
  • Generally few side effects
  • Hypersensitivity if allergic to PCN
  • Mild stomach cramps
  • Nausea/vomiting/diarrhea
  • Yeast overgrowth

22
Aminoglycosides
  • Amikacin
  • Gentamicin
  • Tobramycin
  • Paromomycin
  • Coverage
  • Gram negative bacilli
  • Enterobacteriaceae, Pseudomonas spp., Haemophilus
    influenzae
  • Paromomycin covers protozoa
  • Bactericidal
  • Inhibits bacterial translocation
  • Concentration-dependent killing
  • Concentration of drug (relative to bacteria MIC)
    induces more rapid, and complete, killing of the
    pathogen

23
Aminoglycosides
  • Disadvantages
  • Target concentration
  • Peak and Trough levels
  • Frequent dose changes
  • Side Effects
  • Ototoxicity
  • 2º to vestibular or cochlear damage
  • Nephrotoxic
  • 10-20
  • Neuromuscular blockade
  • Blocks neuromuscular transmission at
    neuromuscular junction
  • Presynaptic (block acetylcholine
    synthesis/release) or Postsynaptic (at motor
    nerve end plate) action
  • Postsynaptic

24
Vancomycin
  • Glycopeptide antibiotic
  • Bacteriostatic
  • Inhibits cell wall synthesis in GPB
  • Use to cover resistant Strep pneumo
  • Synergistic with PCN or Ampicillin
  • Coverage
  • Gram positive bacteria
  • MRSA
  • Coag Neg Staph
  • C.diff
  • Enterococcus
  • Except VRE

25
Vancomycin
  • Renal excretion
  • Side Effects
  • Red-man syndrome
  • Hypotension
  • Steven Johnson Syndrome (SJS)
  • Toxic epidermal necrolysis (TENs)
  • Interstitial nephritis
  • Poor bone and brain penetration
  • 7-13 bone
  • lt10 brain
  • 60/mg/kg
  • Usually 20-40 mg/kg

26
Vancomycin
  • VRE- Vancomycin Resistant Enterococcus
  • Treatment
  • Linezolid (Zyvox)
  • Daptomycin
  • Can not use to treat PNA? surfactant in lung
    breaks down drug
  • Synercid
  • Quinupristin and dalfopristin
  • Enterococcus faecium (not faecalis)

27
Clindamycin
  • Coverage (POIV)
  • Gram positive cocci
  • Staph/Strep
  • Anaerobes
  • Above diaphragm
  • Bacteriostatic
  • But considered bactericidal against
  • Some staph, strep, and B.fragilis
  • Great BONE penetration? 60
  • Linezolid? 50
  • Side Effects
  • Diarrhea
  • Allergic reactions

28
Macrolides
  • Azithromycin
  • Clarithromycin
  • Erythromycin
  • Coverage
  • GPC, Haemophilus spp, Moraxella catarrhalis
  • Atypical Legionella, Chlamydia and Mycoplasma
    pneumoniae
  • Rickettsia, helicobacter, toxoplasma
  • Good tissue and intracellular penetration
  • Long half lives
  • Azithromycin ½ life is 68 hrs

29
Macrolides
  • Side Effects
  • Erythromycin
  • Hypertrophic pyloric stenosis
  • Long QT syndrome
  • Interstitial nephritis
  • Azithromycin
  • Hepatotoxicity- increased LFTs, cholestatic
    jaundice
  • All three (clarithromycin, erythromycin,
    azithromycin)
  • N/V/DIARRHEA
  • Anaphylaxis
  • SJS
  • Pseudomembranous colitis

30
Miscellaneous Antibiotics
  • Tetracycline (POIV)
  • Bacteriostatic
  • GP, GN, rickettsia, mycoplasma, chlamydia,
    spirochete (Borrelia), malaria, tularemia,
    leptospirosis, RMSF
  • Side effects
  • Tooth discoloration
  • Do not take with milk
  • Use in patients gt 8 yo
  • Fluoroquinolones
  • Bactericidal
  • Use if gt18 yo
  • Arthropathy, erosion of cartilage in weight
    bearing joints
  • GNB, GP except MRSA, some pseudomonas, chlamydia,
    mycobacteria
  • Metronidazole (Flagyl)
  • Anaerobes and CNS coverage
  • Below diaphragm

31
CNS INFECTION
32
Bacterial Meningitis Treatment
33
Duration of Treatment
  • Neonate
  • 10-14 days
  • GBS, L.monocytogenes
  • 3 weeks
  • gram-neg enteric meningitis
  • Infant/Child
  • 10-14 days
  • N. meningitides? 7 days
  • H. influenza
  • S. pneumoniae

34
Pneumonia
35
Etiology of Pneumonia in Infants and Children

Viral Agents Para 1,2,3 Influenza A, B. Etc.
Winter Summer
S. Pneumoniae
Mycoplasma
RSV C. Trachomatis CMV
1? Staph
2? Staph
Chlamydia Pneumoniae
Strep.Gr.B E. Coli
H. Inf. b
1 mo 3 mo 6 mo 1 yr
3 yrs 5 yrs 10 yrs
36
Antimicrobial Agents for Community Acquired
Pneumonia in Various Pediatric Age Groups
37
Children with Pneumonia Warranting Consideration
of Inpatient Management
  • Toxic appearance
  • Respiratory distress
  • Pleural effusion
  • Immunocompromised host
  • Progression during outpatient therapy
  • Age factors
  • Less than 3 mos
  • Less than 3 yrs with lobar
  • Less than 5 years with more than 1 lobe
  • Those with chronic disease
  • Pulmonary
  • Cardiac
  • Renal
  • Diabetes
  • Metabolic disorders
  • Anemia
  • malignancies

38
HEMATOGENOUS OSTEOMYELITIS
39
Neonates
40
Infants/ Children
41
Initial Treatment of Osteomyelitis
42
S. aureus Coverage
  • Semi-synthetic PCN
  • Nafcillin or Oxacillin
  • 1st generation cephalosporin
  • 2nd generation cephalosporin
  • Clindamycin/Vancomycin

43
Important Information
  • Treatment less than 3 weeks associated with
    increase risk for recurrence
  • Treatment with IV less than 7 days associated
    with morbidity
  • Total duration of treatment 4-6 weeks
  • Time to stop resolution of symptoms with
    normalized WBC, CRP, or ESR
  • CRP lt 1
  • ESR lt 15

44
The 1 Scary Bug
MRSA
45
Comparison of HA-MRSA and CA-MRSA
46
MRSA
  • In 2005 60 of soft skin tissue infections (SSTI)
    were MRSA
  • Clindamycin resistance at UMC and sunrise? 46
  • 6? 26? 46 (in 2009)
  • Alternative treatment
  • Vancomycin- slow so add gentamicin for synergy
  • Since it can still be MSSA.add Nafcillin or
    Oxacillin

47
MRSA Treatment
  • Outpatient
  • Tetracycline
  • Bactrim
  • Clindamycin
  • Inpatient
  • Clindamycin
  • Vancomycin
  • Linezolid
  • Daptomycin
  • Synercid
  • Quinupristin and dalfopristin

48
CA-MRSA Antibiotic Susceptibility
  • Vancomycin
  • Gentamicin/rifampin (synergy 3-5 days)
  • Trimethoprim-sulfamethoxazole
  • Clindamycin
  • Doxycycline/minocycline
  • Linezolid (Zyvox)
  • Daptomycin (Cubicin)
  • Quinupristin/dalfopristin (Synercid)

49
(No Transcript)
50
Infectious Disease Clinics. Infect Dis Clin N Am
19 (2005) 747-757
51
Board Review
  • You admit an 18yo boy to the hospital with RLL
    PNA. While gathering your history, you discover
    that 4 years ago he developed a rash and
    respiratory difficulty when he received IM
    ceftriaxone. Of the following, the BEST
    antimicrobial agent for this patient is
  • Ceftriaxone
  • Levofloxacin
  • Meropenem
  • Penicillin

52
Board Review
  • You admit an 18yo boy to the hospital with RLL
    PNA. While gathering your history, you discover
    that 4 years ago he developed a rash and
    respiratory difficulty when he received IM
    ceftriaxone. Of the following, the BEST
    antimicrobial agent for this patient is
  • Ceftriaxone
  • Levofloxacin
  • Meropenem
  • Penicillin

53
Board Review
  • Levofloxacin has broad spectrum activity against
    bacteria that cause LRTI, including GPB, GNB,and
    atypicals.
  • He had a previous reaction to ceftriaxone
  • Meropenem rarely needed for CA-PNA
  • Vancomycin monotherapy does not provide broad
    coverage of potential organisms

54
Board Review
  • You are planning to treat a patient who has a PCN
    allergy with clarithromycin. The mother asks you
    about possible adverse effects of this
    medication. Of the following adverse effects,
    the MOST likely to expect is
  • Diarrhea
  • Dizziness
  • Headache
  • Torsade's de points
  • Urticaria

55
Board Review
  • You are planning to treat a patient who has a PCN
    allergy with clarithromycin. The mother asks you
    about possible adverse effects of this
    medication. Of the following adverse effects,
    the MOST likely to expect is
  • Diarrhea
  • Dizziness
  • Headache
  • Torsade's de points
  • Urticaria

56
Board Review
  • A 3 yo patient who has ALL is admitted to the
    PICU after developing severe sepsis 2º to
    Pseudomonas aeruginosa. She is intubated,
    ventilated, and requires intensive vasopressor
    support. Of the following, the MOST appropriate
    antibiotic regimen for the treatment of this
    patient is an aminoglycoside plus
  • Cefazolin
  • Cefdinir
  • Ceftazidime
  • Ceftriaxone
  • Cefuroxime

57
Board Review
  • A 3 yo patient who has ALL is admitted to the
    PICU after developing severe sepsis 2º to
    Pseudomonas aeruginosa. She is intubated,
    ventilated, and requires intensive vasopressor
    support. Of the following, the MOST appropriate
    antibiotic regimen for the treatment of this
    patient is an aminoglycoside plus
  • Cefazolin
  • Cefdinir
  • Ceftazidime
  • Ceftriaxone
  • Cefuroxime

58
Board Review
  • A 5 yo boy who has neuroblastoma is admitted to
    the PICU for treatment of fever, neutropenia, and
    severe hypotension, due to Klebsiella pneumoniae
    sepsis. Over the last several months, he has
    received multiple courses of vancomycin,
    ceftazidime to treat fever and neutropenia.
    Antibiotic susceptibility testing of the pathogen
    shows it to be susceptible to carbapenem and
    aminoglycoside classes of antibiotics. Of the
    following, the MOST likely mechanism of
    resistance in this organism is
  • Alterations in penicillin-binding proteins
  • Decreased affinity for ribosomal target binding
    sites
  • Increased thickness for organism cell wall
  • Production of an efflux pump
  • Production of extended spectrum beta-lactamases

59
Board Review
  • A 5 yo boy who has neuroblastoma is admitted to
    the PICU for treatment of fever, neutropenia, and
    severe hypotension, due to Klebsiella pneumoniae
    sepsis. Over the last several months, he has
    received multiple courses of vancomycin,
    ceftazidime to treat fever and neutropenia.
    Antibiotic susceptibility testing of the pathogen
    shows it to be susceptible to carbapenem and
    aminoglycoside classes of antibiotics. Of the
    following, the MOST likely mechanism of
    resistance in this organism is
  • Alterations in penicillin-binding proteins
  • Decreased affinity for ribosomal target binding
    sites
  • Increased thickness for organism cell wall
  • Production of an efflux pump
  • Production of extended spectrum beta-lactamases

60
Board Review
  • A 15 yo boy who has Mycoplasma pneumoniae is
    being treated with azithromycin. Of the
    following, the MOST likely adverse reaction would
    be
  • Anorexia
  • Diarrhea
  • Dyspepsia
  • Headache
  • Rash

61
Board Review
  • A 15 yo boy who has Mycoplasma pneumoniae is
    being treated with azithromycin. Of the
    following, the MOST likely adverse reaction would
    be
  • Anorexia
  • Diarrhea
  • Dyspepsia
  • Headache
  • Rash

62
Thank You
  • Dr. Pisespong Patamasucon

63
THE END
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